U.S. patent number 3,954,967 [Application Number 05/459,673] was granted by the patent office on 1976-05-04 for method of producing microcolloidal aqueous emulsions of unsaturated organic insecticidal compounds.
This patent grant is currently assigned to Vanguard Chemical Company, Inc.. Invention is credited to John T. Urton.
United States Patent |
3,954,967 |
Urton |
May 4, 1976 |
Method of producing microcolloidal aqueous emulsions of unsaturated
organic insecticidal compounds
Abstract
A method of reducing the micelle size of an aqueous emulsion of
an unsaturated organic compound utilizes an ionic pumping action to
achieve micelle division. The resin utilized is selected on the
basis of the presence in the molecular chain of a high number of
sites which can accept a positive ion to cause the molecule to
assume an overall charge. A gross emulsion is first formed
utilizing a sufficient quantity of surfactant so that an excess is
present to assure surfacating of the newly formed micelles upon
division of the micelles of the initial emulsion. The resin is
equilibrated utilizing a compound capable of donating positive ions
to the resin molecule to cause the molecule to assume a charge of
the same sign as the sign of the charge on the emulsion micelles.
The resulting increased charge in the emulsion results in division
of the micelles into micelles of a smaller size. The resin pumping
action can be continued until the micelles of the emulsion are
characterized by an inability to reflect light of a visible
wavelength.
Inventors: |
Urton; John T. (Prairie
Village, KS) |
Assignee: |
Vanguard Chemical Company, Inc.
(Kansas City, MO)
|
Family
ID: |
26864899 |
Appl.
No.: |
05/459,673 |
Filed: |
April 10, 1974 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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169248 |
Aug 5, 1971 |
3813345 |
|
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Current U.S.
Class: |
424/78.18;
424/78.24; 424/78.28; 424/78.29; 514/68; 514/365; 514/481; 514/530;
514/531; 514/551; 514/755; 514/937; 525/301; 424/78.22;
424/777 |
Current CPC
Class: |
A01N
25/04 (20130101); Y10S 514/937 (20130101) |
Current International
Class: |
A01N
25/04 (20060101); A61K 031/78 (); A01N 009/20 ();
A01N 009/30 () |
Field of
Search: |
;424/78,80,81,300,306 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Chemical Abstracts, Vol. 71, (1969), p. 128756j..
|
Primary Examiner: Turner; V. D.
Attorney, Agent or Firm: Lowe, Kokjer, Kircher, Wharton
& Bowman
Parent Case Text
This is a division of prior application Ser. No. 169,248, filed
Aug. 5, 1971, now U.S. Pat. No. 3,813,345.
Claims
Having thus described the invention what is claimed as new and
desired to be secured by Letters Patent is:
1. A method of reducing the micelle size of an aqueous emulsion of
an unsaturated organic compound having insecticidal properties,
said compound being characterized by solubility in an organic polar
solvent, and an absence of the elements iron, copper, zinc and
phosphorous, said method comprising the steps of:
preparing the internal phase of said emulsion by adding a quantity
of said compound along with a quantity of surfactant to an organic
polar solvent,
said compound being present in a quantity such that the volume of
the compound relative to the volume of the subsequently formed
emulsion is no more than approximately 4%, and said solvent being
present in a quantity such that the volume of the solvent relative
to the volume of the subsequently formed emulsion is from 10% to
25%,
said surfactant being characterized by the ability to form a
microemulsion which is soluble in said polar solvent and said
surfactant being present in a quantity of at least approximately
two parts by volume of said surfactant to one part by volume of
said compound;
diluting said internal phase to at least approximately 70% by
volume water to form said emulsion;
adding to said emulsion a quantity of a water soluble resinous
compound to comprise at least approximately 0.005% by weight of the
subsequently formed microemulsion characterized by the presence of
a high number of positive ion accepting sites in each molecule of
the resinous compound, there being at least one site in each
repeating monomer of the molecule;
equilibrating said resinous compound with a stoichiometric quantity
of a compound capable of donating positive ions to said sites to
cause the latter to assume a charge of the same sign as the sign of
the charge on the emulsion micelle while maintaining a
substantially constant pH in said emulsion;
whereby the increased charge in the emulsion from the molecules of
the resinous compound results in division of the emulsion micelles
into micelles of a smaller size to form a microemulsion; and
incorporating in the emulsion a chelating agent for the calcium
ions present in the basil membrane of an insect to thereby increase
the penetrability of said organic compound through said insect.
2. The method as set forth in claim 1, wherein said step of
incorporating a chelating agent comprises utilizing dimethyl
sulfoxide as the polar solvent for preparing said internal
phase.
3. The method as set forth in claim 1, wherein said step of
incorporating a chelating agent comprises adding to the emulsion a
quantity of ethylenediaminetetraacetic acid.
4. A method of reducing the micelle size of an aqueous emulsion of
an unsaturated organic compound having insecticidal properties,
said compound being characterized by solubility in a polar solvent,
and an absence of the elements iron, copper, zinc and phosphorous,
said method comprising the steps of:
preparing the internal phase of said emulsion by dissolving a
quantity of said compound in an organic polar solvent, adding a
quantity of surfactant to the resulting solution, and mixing of the
surfactant and the solution,
said compound being present in a quantity such that the volume of
the compound relative to the volume of the subsequently formed
emulsion is no more than approximately 4%, and said solvent being
present in a quantity such that the volume of the solvent relative
to the volume of the subsequently formed emulsion is from 10% to
25%,
said surfactant being characterized by the ability to form a
microemulsion which is soluble in said polar solvent and said
surfactant being present in a quantity of at least approximately
two parts by volume of said surfactant to one part by volume of
said compound;
adding to said internal phase a quantity of a water soluble
resinous compound selected from the group consisting of polyacrylic
acid and pyrrolidone polymers in a quantity of at least 0.005% by
weight of the subsequently formed microemulsion;
diluting said internal phase to at least approximately 70% by
volume water to form said emulsion;
adding to said emulsion a second quantity, comprising at least
0.005% by weight of the subsequently formed microemulsion, of said
resinous compound; and
equilibrating said resinous compound with a stoichiometric quantity
of a compound capable of donating a positive ion to the acid
radical of said polyacrylic acid or to the amide radical of said
pyrrolidone to cause the radical to assume a charge of the same
sign as the sign of the charge on the emulsion micelles,
said equlibrating step comprising equilibrating said resinous
compound with a compound selected from the group consisting of
sodium hydroxide, ammonium hydroxide, triethanolamine,
monoethanolamine, and diisopropanolamine when said resinous
compound is a polyacrylic acid polymer, and wherein said
equilibrating step comprises equilibrating said resinous compound
with hydrochloric acid when said resinous compound is a pyrrolidone
polymer,
said equilibrating step including the step of maintaining a
substantially constant pH in the emulsion,
whereby the increased charge in the emulsion from the molecules of
said resinous compound results in division of the emulsion micelles
into micelles of a smaller size to form a microemulsion; and
incorporating in the emulsion a chelating agent for the calcium
ions present in the basil membrane of an insect to thereby increase
the penetrability of said organic compound through said insect.
5. A method of reducing the micelle size of an aqueous emulsion of
an unsaturated organic compound having insecticidal properties said
compound being characterized by solubility in a polar solvent, and
an absence of the elements iron, copper, zinc and phosphorous, said
method comprising the steps of:
dissolving a quantity of said compound in a polar solvent;
said compound being present in a quantity such that the volume of
the compound relative to the volume of the subsequently formed
emulsion is no more than approximately 4%, and said solvent being
present in a quantity such that the volume of the solvent relative
to the volume of the subsequently formed emulsion is from 10% to
25%;
adding to the resulting solution a surfactant capable of forming a
microemulsion which is soluble in the solution, in a quantity of at
least approximately two parts by volume of said surfactant to one
part by volume of said compound;
mixing said surfactant and the solution to form an internal
phase;
adding to said emulsion a second quantity, comprising at least
0.005% by weight of the subsequently formed microemulsion, of a
water soluble resinous compound characterized by the presence of a
high number of positive ion accepting sites in each molecule of the
resinous compound;
equilibrating said resinous compounds with a stoichiometric
quantity of a compound capable of donating positive ions to said
sites to cause the latter to assume a charge of the same sign as
the sign of the charge on the emulsion micelles, while maintaining
a substantially constant pH in the emulsion,
whereby the increased charge in the emulsion from the molecules of
the resinous compounds results in division of the emulsion micelles
into micelles of a smaller size to form a microemulsion;
continuing said equilibrating step until the resulting micelles of
a smaller size are characterized by an inability to reflect light
of a visible wavelength; and
incorporating in the emulsion a chelating agent for the calcium
ions present in the basil membrane of an insect to thereby increase
the penetrability of said organic compound through said insect.
6. The method as set forth in claim 5, wherein said organic
compound comprises pyrethrin, said dissolving step comprises
dissolving a quantity of said pyrethrin in methyl alcohol; and
including the additional step of adding a quantity of
betahydroxytoluene to the solution, said step of adding a first
quantity of a resinous compound comprising adding a quantity of a
polyacrylic acid polymer to said internal phase, said step of
incorporating a chelating agent comprising adding a quantity of
ethylenediaminetetraacetic acid to the emulsion, and said
equilibrating step comprising adding a quantity of sodium hydroxide
to the emulsion.
7. The method as set forth in claim 5, wherein said organic
compound comprises l-naphthyl N-methyl carbamate, said dissolving
step comprises dissolving a quantity of said l-naphthyl N-methyl
carbamate in a solution of approximately 40% by volume dimethyl
sulfoxide and approximately 60% by volume methyl alcohol, said step
of adding a surfactant comprising adding a quantity of
polyoxyethylene sorbitan monostearate, said step of adding a first
quantity of a resinous compound comprising adding a quantity of a
polyacrylic acid polymer to said internal phase, said step of
incorporating a chelating agent comprising adding a quantity of
ethylenediaminetetraacetic acid to the emulsion, and said
equilibrating step comprising adding a quantity of sodium hydroxide
to the emulsion.
8. The method as set forth in claim 7, wherein there is included
the step of adjusting the pH of said polyacrylic acid to
approximately 6.8 before the same is added to said internal
phase.
9. A method of killing insects comprising the steps of:
preparing the internal phase of an aqueous emulsion of an
unsaturated organic insecticidal compound, said compound being
characterized by solubility in a polar solvent, and an absence of
the elements iron, copper, zinc and phosphorous, by adding a
quantity of said compound along with a quantity of surfactant to an
organic polar solvent, said compound being present in a quantity
such that the volume of the compound relative to the volume of the
subsequently formed emulsion is no more than approximately 4%, and
said solvent being present in a quantity such that the volume of
the solvent relative to the volume of the subsequently formed
emulsion is from 10% to 25%,
said surfactant being characterized by the ability to form a
microemulsion which is soluble in said polar solvent and said
surfactant being present in a quantity of at least approximately
two parts by volume of said surfactant to one part by volume of
said compound;
diluting said internal phase to at least approximately 70% by
volume water to form said emulsion;
adding to the emulsion a quantity of a water soluble resinous
compound to comprise at least approximately 0.005% by weight of the
subsequently formed microemulsion characterized by the presence of
a high number of positive ion accepting sites in each molecule of
the resinous compound, there being at least one site in each
repeating monomer of the molecule;
incorporating in the emulsion a chelating agent for the calcium
ions present in the basil membrane of an insect to increase the
penetrability of said insecticidal compound through said
insect;
equilibrating said resinous compound with a stoichiometric quantity
of a compound capable of donating positive ions to said sites to
cause the latter to assume a charge of the same sign as the sign of
the charge on the emulsion micelles without substantial change in
the pH of the emulison, to increase the charge in the emulsion from
the molecules of the resinous compound and thereby effect division
of the emulsion micelles into micelles of a smaller size; and
applying the equilibrated emulsion to an area where an insect will
come into contact therewith.
10. A method of killing insects comprising the steps of:
preparing the internal phase of an aqueous emulsion of an
unsaturated organic insecticidal compound, said compound being
characterized by solubility in a polar solvent, and an absence of
the elements iron, copper, zinc and phosphorous by adding a
quantity of said compound along with a quantity of surfactant to an
organic polar solvent, said compound being present in a quantity
such that the volume of the compound relative to the volume of the
subsequently formed emulsion is no more than approximately 4%, and
said solvent being present in a quantity such that the volume of
the solvent relative to the volume of the subsequently formed
emulsion is from 10% to 25%,
said surfactant being characterized by the ability to form a
microemulsion which is soluble in said polar solvent and said
surfactant being present in a quantity of at least approximately
two parts by volume of said surfactant to one part by volume of
said compound;
diluting said internal phase to at least approximately 70% by
volume water to form said emulsion;
incorporating in the emulsion a chelating agent for the calcium
ions present in the basil membrane of an insect to increase the
penetrability of said insecticidal compound through said instect;
and
applying said emulsion to an area where an insect will come into
contact therewith.
11. A method of increasing the efficacy of an insecticidal
compound, wherein said compound is an unsaturated organic compound
characterized by solubility in an organic polar solvent and an
absence of the elements iron, copper, zinc and phosphorous, said
method comprising the steps of:
preparing an aqueous solution of a water soluble polyacrylic acid
polymer;
partially equilibrating said polymer with a less than
stoichiometric quantity of a base capable of reacting with the
carboxyl groups of the polymer to yield water and a substituted
polymer molecule;
further equilibrating said polymer with a less than stoichiometric
quantity of an amine selected from the group consisting of
triamylamine, triethylamine, and di-(2-ethylhexyl)amine;
preparing a solution of said compound by adding a quantity of said
compound along with a quantity of surfactant to an organic polar
solvent, said compound being present in a quantity such that the
volume of the compound relative to the volume of the subsequently
formed emulsion is no more than approximately 4%, and said solvent
being present in a quantity such that the volume of the solvent
relative to the volume of the subsequently formed emulsion is from
10% to 25%,
said surfactant being characterized by the ability to form a
microemulsion which is soluble in said polar solvent and said
surfactant being present in a quantity of at least approximately
two parts by volume of said surfactant to one part by volume of
said compound; and
combining said solutions to form an aqueous emulsion.
12. The method as set forth in claim 11, including the steps
of:
adding a saline solution to said emulsion to precipitate a complex
comprising said compound and the substituted polymer; and
removing said precipitate from the supernatant liquid.
13. The method as set forth in claim 12, wherein there is included
the step of drying said precipitate to powder form.
14. The method as set forth in claim 12, wherein the step of
preparing the aqueous solution comprises preparing said solution in
a concentration of from 0.1 to 0.3% by weight of said polymer.
Description
The invention also provides for a method of killing insects wherein
a microemulsion of an unsaturated organic compound having
insecticidal properties is prepared in the manner set forth above.
An additional step is the inclusion of a chelating agent for the
calcium ions which are present in the basil membrane of an insect.
This allows the emulsion micelles of the insecticide to penetrate
through the insect.
The invention relates to the formation of aqueous emulsions and,
more particularly, to a method of forming an aqueous emulsion
having a reduced micelle size and to a method of utilizing
emulsions of a decreased micelle size to increase the efficacy of
biologically active compounds.
In many instances it is desirable to utilize an aqueous emulsion of
an organic compound rather than dissolve the compound in an organic
solvent. The ability to substitute an aqueous emulsion for an
organic solvent is, however, limited by the size of the emulsion
micelles. Where micelle size is critical, an emulsion cannot be
satisfactorily substituted for a solution because the emulsion
micelles are much larger in size than the molecules of a solution.
For example, with water insoluble biologically active compounds,
efficacy is directly proportional to the quantity of molecules
available for reaction. Manifestly, if an aqueous emulsion could be
provided wherein the emulsion micelles were of a size approaching
that of molecules, the aqueous emulsion could be utilized with
efficacy approaching that possible with an organic solvent.
Additionally, while there are many obvious advantages in using a
water base system, including availability and ease of handling, one
of the most important considerations is the ecological impact. In
recent years some biologically active compounds useful as
herbicides, fungicides, and insecticides have been substantially
limited in use or banned completely because of their harmful
effects on the soil, the atmosphere, and mammalian toxicity. Often,
however, the aforementioned harmful effects are attributable not to
the active compound itself, but to the organic solvent, such as
petroleum distillate, which is the solvent used to extract the
compound.
While there have been previous attempts to form microemulsions
wherein the micelle size is greatly reduced, these have been
limited to the formation of gels which, when diluted out, broke to
cloudy emulsions. While this in itself would prevent such a system
from being useful with biologically active compounds on a large
scale, another limitation of the microemulsion gels is the presence
of a large excess of surfactant in the interphase which could cause
phytotoxicity.
It is therefore an object of the present invention to provide a
method of preparing emulsions of unsaturated organic compounds
wherein sufficiently dilute concentrations of both the organic
compound and any organic solvent in which it may be dissolved are
possible so as to avoid the disadvantages associated with organic
solvents and active compounds.
As a corollary to the above object, an important aim of the
invention is to provide a method of preparing aqueous emulsions
wherein the emulsion micelles are of a size approaching that of
molecules in solution whereby the emulsion is similar in both
physical properties and chemical activity to a true solution.
An important aim of this invention is also to provide a method of
preparing an emulsion wherein the emulsion micelles are of a
sufficiently small size that no Tyndell beam effect is observable
in the visible light range thus evidencing the small size of the
micelles.
An important object of this invention is to provide a method of
forming an emulsion wherein the emulsion micelles are of a reduced
size, as set forth in the above object, and the presence of excess
surfactant in the external phase is avoided thus avoiding any
possible harmful effects such as phytotoxicity from the excess
surfactant.
Another object of the invention is to provide a method of forming
an emulsion of biologically active compounds wherein a protective
resin covering increases the stability of the compound and the
protective covering is biodegradible so as not to interfere with
the efficacy of the compound.
An objective of the invention is also to provide a method of
forming aqueous emulsions wherein the presence of a resin material
in the external phase of the emulsion prevents freezing far below
the freezing point of water.
Another one of the objectives of my invention is to provide a
method for preparing aqueous emulsions of biologically active
compounds wherein the presence of a resinous compound which is
utilized to reduce the micelle size of the emulsion results in
better adhesion of the active compound to plants as a result of the
close van der Waals' forces which are established with the plant
cutin.
As a corollary to the above objective, another important object of
the invention is to improve the adhesion of biologically active
compounds to plants, and to simultaneously improve the adhesion of
the active compound to an insect coming in contact therewith as a
result of the formation of strong association bonds between the
resin and the proteinaceous chitin or exoskeleton of the insects to
thereby assure removal of the active compound from the plant by the
insect.
It is also an aim of the present invention to provide a method for
preparing aqueous emulsions wherein the emulsion micelles are of a
substantially reduced size and this reduction in size is achieved
by physiochemical effects thereby eliminating the need for
expensive mechanical equipment.
Still another object of the invention is a method of preparing
aqueous emulsions of unsaturated organic compounds wherein the
micelle size of the emulsion is substantially reduced and wherein
this reduction in size is achieved without chemical change of the
organic compound.
An important objective of the present invention is to provide a
method of preparing aqueous emulsions of biologically active
compounds wherein the efficacy of the compounds is greatly
increased over that possible with ordinary gross emulsions as a
result of the increased penetrability of the emulsion micelles of a
reduced size and the increased geometric surface area which is
available for reaction.
As a corollary to the above object, this invention has as one of
its objectives, the provision of a method of preparing aqueous
emulsions of biologically active compounds wherein the efficacy of
the compounds is increased to such an extent that the quantity of
the compound utilized can be reduced thereby reducing the total
cost and any possible adverse effects attributable to the
compound.
Still another corollary to the object second above is to provide a
method of increasing the efficacy of biologically active compounds
whereby known compounds which have a lower level of activity but
are also less likely to be harmful can be substituted for more
active but potentially more harmful compounds.
Yet another object of this invention is a method of preparing an
aqueous emulsion of biologically active compounds wherein the
emulsion micelles are of a greatly reduced size, thereby resulting
in increased efficacy of the compounds to a point where extraction
of the compounds with potentially harmful organic solvents, such as
petroleum distillate, can be avoided by extracting the compounds
with less harmful solvents, such as alcohol.
It is also an aim of this invention to provide a method of
preparing aqueous emulsions of organic compounds as described in
the foregoing objects, which method is applicable to a large number
of compounds, for example biologically active compounds formed from
oleo resinous and natural carboxylic chemicals, chlorinated
hydrocarbons, water insoluble phenolics, carbamates, quinone and
quinoline hydrocarbons, thiol hydrocarbons; benzene and analine
water insoluble dies; water insoluble aromatic oils; and water
insoluble antioxidants.
An important object of this invention is also to provide a method
of preparing microemulsions of organic compounds wherein a resinous
pumping action is utilized to decrease the size of the emulsion
micelles and wherein the presence of the resin increases the
stability of the compound as a result of the protection from alkali
and acid hydrolysis, as well as oxidation, which the resin
affords.
Another reason for the ineffectiveness of certain known
biologically active compounds is that they are so reactive, either
in solution or in an ordinary emulsion that they react with the
environment before they actually enter a living organism which they
are intended to act upon. It is therefore, another very important
object of this invention to provide a method of forming an emulsion
of biologically active compounds wherein the compound is protected
from reaction with its environment by a resinous coating thereby
greatly increasing the efficacy of the compound against the living
organism on which it is intended to act.
An aim of this invention is also to provide a method of reducing
the micelle size of aqueous emulsions without utilizing heat and
thereby avoiding possible deleterious effects of the latter upon
the internal emulsion phase.
This invention has, as another important aim, the provision of a
method of reducing the micelle size of aqueous emulsions wherein
the resulting microemulsions can be diluted out to very small
concentrations without danger of breaking the emulsion thereby
making the microemulsion system widely applicable for use with
biologically active compounds.
It is also an important object of this invention to provide a
method of killing insects wherein the efficacy of an insecticide is
greatly increased by incorporating in the insecticide a chelating
agent for the calcium ions present in the basil membrane of an
insect thereby preventing these ions from blocking passage of the
insecticide through this membrane.
A further aim of this invention is to provide a method of reducing
the micelle size of aqueous emulsions of organic compounds to
achieve superior penetration through wood for protecting live wood
against insects and disease and for protecting dead wood against
insects and deterioration in general.
BACKGROUND OF THE INVENTION
It has been reported (Schulman and Montague, Annals of the New York
Academy of Science, Vol. 92, p. 336 (1961)) that it is necessary to
produce negative interfacial tension between the emulsion micelles
(internal phase) and the external phase (water) of an aqueous
emulsion in order to achieve division of the micelles into micelles
of a smaller size.
This negative interfacial tension has been defined in terms of the
equation:
where
.gamma..sub.i = interfacial surface tension
.gamma..sub.o/w = oil-water interfacial tension in the absence of a
surfactant
.pi. = spreading pressure of the surfactant at the oil-water
interface
Manifestly, either an increase in .pi. or a decrease in
.gamma..sub.o/w will result in a negative value for .gamma..sub.i
thus resulting in division of the emulsion micelles into micelles
of a smaller size.
The present invention is best understood when equation A is
expanded to describe in greater detail the forces which affect the
value of .gamma..sub.i. This expanded equation is represented as
follows:
the forces F.sub.1 through F.sub.6 are represented schematically in
FIG. 1 of the drawing wherein an emulsion micelle comprising the
internal phase of an emulsion is designated generally by the
numeral 10. The emulsion micelle is comprised of molecules of a
hydrocarbon 12 which is water insoluble. The hydrocarbon 12 is
represented by four small circles enclosed within a large circle
and it is to be understood that the smaller circles are merely
representative of the presence of the hydrocarbon and are not
intended to indicate hydrocarbon molecules. Disposed around the
outer periphery of the micelle 10 are a plurality of surfactant
molecules 14. Each molecule 14 is comprised of a lipophilic end 16,
a hydrophilic end 18, and a connecting chain 20 (FIG. 1). The
lipophilic end 16 is soluble in the hydrocarbon 12 and the
hydrophilic end 18 is soluble in the external aqueous phase which
is represented generally by the numeral 22 and is comprised of a
plurality of water molecules 24. A certain number of surfactant
molecules 14, which have not yet found their way into the internal
phase are also present in the external phase 22. In general, the
surfactant molecules 14 may be of the nonionic, cationic or anionic
type although it is preferable, as will be explained in greater
detail hereinafter, to utilize a nonionic surfactant in combination
with a small quantity of an anionic surfactant. Assuming the
anionic surfactant is in the form of a sodium salt, the sodium ions
will migrate toward the negative charge layer, which is thought to
be a static charge, surrounding the micelle 10 and indicated by a
broken line in FIGS. 1-3.
Referring again to equation B and to FIG. 1, the forces F.sub.1
through F.sub.6 are defined as follows:
F.sub.1 = HC.sub.ch = cohesive force between the hydrocarbon
molecules
F.sub.2 = (S.sub.lp.sup.. HC.sub.ah) = adhesive attraction between
the lipophilic end of the surfactant and the molecules of the
hydrocarbon
F.sub.3 = LP.sub.ch = cohesive force between the lipophilic ends of
the surfactant molecules
F.sub.4 = (S.sub.hp.sup.. W.sub.ah) = adhesive attraction between
the hydrophilic ends of the surfactant and the water molecules
F.sub.5 = S.sub.hpch = cohesive force between the hydrophilic ends
of the surfactant molecules
F.sub.6 = W.sub.ch = cohesive force between the water molecules
Transferring the above representations for F.sub.1 through F.sub.6
to equation B yields an equation:
for the interfacial tension of an aqueous emulsion.
Prior attempts to reduce the micelle size of aqueous emulsions
have, in part, been directed to adding large quantities of a
nonionic surfactant with a low hydrophilic-lipophilic balance
number. This lowers the factor S.sub.hp.sup.. W.sub.ah (F.sub.4) in
equation (C) and causes the overall factor of .gamma..sub.o/w
(equation B) to be reduced. This causes .gamma..sub.i to assume a
negative value and results in further micelle division. Since
surfactants of this type are largely water insoluble, dilution of
the emulsion is not possible and the technique can be used
successfully only where a gel is an acceptable end product. Another
disadvantage of utilizing a large excess of such a surfactant is
that the surfactant molecules eventually become so crowded around
the outside of the micelle that compaction occurs and the factor
S.sub.lpch (F.sub.3) dominates all others thereby preventing
.gamma..sub.i from assuming a negative value and limiting the
extent to which further reduction in micelle size can occur.
Still another known technique for reducing the micelle size of an
emulsion is the application of heat. This can be utilized when the
forces of compaction prevent further micelle division by the
addition of more surfactant. Heat causes the van der Waals' forces
to be temporarily broken and the value of S.sub.hp.sup.. W.sub.ah
(F.sub.4) in equation (C) to be reduced to give .gamma..sub.i a
negative value and the emulsion micelles to undergo further
division. This technique cannot be utilized with many compounds,
however, because of the danger of decomposition from heating. Thus,
most biologically active compounds are exempt from this
procedure.
A third known method of reducing the micelle size of an emulsion is
to introduce medium chain length fatty acids or alcohols into the
emulsion. This tends to break or damp the van der Waals' forces,
decreasing the values of S.sub.hpch (F.sub.5) and S.sub.lpch
(F.sub.3) in equation (C). This technique is also limited in the
extent to which it can reduce the micelle size and is not
applicable to dilute aqueous emulsions because of the water
insolubility of the fatty acids and alcohols used.
To avoid the disadvantages of the prior art methods discussed above
and yet achieve a dilute aqueous emulsion of an unsaturated organic
compound characterized by emulsion micelles of a size approaching
that of molecules in solution, it has been found that a polyanionic
or polycationic water soluble resinous compound can be utilized as
a "pumping agent." To achieve micelle size reduction without
encountering the limiting factor of compaction as discussed above,
the resinous compound is introduced to form a relatively stationary
external phase charge situation. The resin thereby achieves a
reduction in the interfacial tension without actually becoming a
part of the interface between the internal phase (emulsion
micelles) and the aqueous external phase.
Referring to FIG. 2 of the drawing, the emulsion micelle 10 is
disposed in the aqueous external phase 22 as previously described
with a plurality of surfactant molecules 14 surrounding the micelle
10. A quantity of a polyacrylic acid polymer represented by the
formula RCO.sub.2 H is disposed in the external phase 22, with each
molecule of the polymer being designated by the numeral 26. It is
to be understood, of course, that the formula RCO.sub.2 H for the
molecules 26 is only representative of the actual formula for the
molecules which would have a molecular weight in the range of from
250,000 to 3,000,000 with an enormous number of COOH groups in each
molecule. When NaOH is added to the emulsion the following reaction
occurs: ##EQU1## with a loose association bond between the Na.sup.+
ions and the negative oxygen of the CO.sub.2.sup.- radical
resulting in an overall negative charge on the repeating resin
group RCO.sub.2. As NaOH continues to be added more and more of the
repeating groups in the polymer chain will become charged while the
pH of the emulsion will remain relatively constant because of the
OH.sup.- ions from the NaOH combining with the displaced H.sup.+
ions from the resin to form water.
The resulting increased charge in the external phase of the
emulsion will cause division of the micelle 10 as a result of the
following forces. First, the repulsive charge forces F.sub.7a and
F.sub.7b (FIG. 2) between the overall negatively charged resin
molecules 26 and the negative charge layer surrounding the micelle
10, and the similar repulsive charge between the Na.sup.+ ions
associated with the polymer acid groups and the Na.sup.+ ions which
surround the micelle 10, act as a positive charge pressure which is
a counter force to the water interfacial tension. Second, because
of the attractive force F.sub.8 between the polar water molecules
24 and the charged resin molecules 26, the former will tend to
migrate toward the latter, thereby reducing the attraction between
the water molecules 24 and any surfactant molecules 14 which are
present in the external phase. This in turn frees the molecules 14
to enter the micelle 10 as a result of their lipophilic attraction
for the latter. The result is an increase in the value of
S.sub.lp.sup.. HC.sub.ah (F.sub.2) (equations B and C above) which
contributes to a negative value for .gamma..sub.i. Third, the
migration of H.sub.2 O molecules 24 to the charged resin molecules
26 removes the former from the surface of the micelle 10 decreasing
the value of S.sub.hp.sup.. W.sub.ah (F.sub.4). Fourth, it is
thought that the presence of the charged resin molecules 26 also
decreases the factor W.sub.ch (F.sub.6) which further lowers the
value of .gamma..sub.i.
With all of the various factors working to reduce .gamma..sub.i,
the latter assumes a negative value and the micelles 10 divide into
micelles 28 of a smaller size as indicated in FIG. 3. Division will
continue until the increased surface area of the micelles 28 causes
the surface tension to increase until .gamma..sub.i reaches zero
and equilibrium exists.
DETAILED DESCRIPTION OF THE INVENTION
It has been found that aqueous emulsions of water insoluble
unsaturated organic compounds can be prepared wherein the emulsion
micelles are of a size approaching that of the molecules in
solution. By "unsaturated organic compounds" is meant compounds
wherein one or more carbon atoms are unsaturated with hydrogen
atoms either as a result of multiple bonding or the presence of a
substitute group. The compounds may be either aliphatic or
aromatic, but in either case it is necessary that the compound be
soluble in a polar solvent and that there be an absence of any of
the elements iron, copper, zinc and phosphorus in the molecule. The
unsaturated compounds which can be most effectively utilized in the
invention generally fall within the molecular weight range of
approximately 120 to 600. Examples of compounds which can be
utilized in the invention include the following: oleoresinous and
natural carboxylic compounds such as pyrethrin, cinneramic acid,
pyrethrosin, monocarboxylic acids, crysanthmic acid, allethrin,
dimethrin, oil of terpentine, terpinene, terpineol, terpinol,
geraniol esters, citrolellol, dipentene, sesquiterpenes, asafetida,
and aspidium; chlorinated hydrocarbons such as perthane,
chlorodane, aldrin, dyrene, isodhen, heptachlor, toxaphene,
chlorobendazide, chloroanil, endrin, parachlorophenoxyacetate,
dichlorophenoxy propionic acid, orthochlorobenzene, neotan,
dichlorodiphenyltrichloroethane, rhothane, ovex, and dichlone;
water insoluble phenolics such as thymol, thyme oil,
thymolphthalein, thymoquinone, allylphenol, methyl resorcinol,
resorcinol monoacetate, resorcyclic acid, piperonyl cyclonene,
dimethylphthalate, and creslyic acid; carbamate compounds such as
carbaryl 1-naphthyl N-methylcarbamate), benomyl methyl
1-butylcarbamoyl-2-benzimidazolecarbamate, methyl naphthyl
carbamate, solan, thanite, isopropyl N-(3-chlorophenyl) carbamate,
"MGK 264" (C.sub.17 H.sub.23 O.sub.2 N), oil of myrbane, and
binapacryl; quinonine and quinoline type compounds such as
8-hydroxyquinoline, 5-hydroxynaphthalquinone, dichlone, quinoidine,
quininone, quinoline, quinolinic acid, quinone, quinovin,
anthraquinone, ethyoxyquin, diphacinone, and methyl eugenol; thiol
type compounds such as thianaphthalene, thiazole, sulfathiazole,
thioacetaldehyde, thiocreosol, thioglycerol, thiolutin antibiotic,
thionalide, thionine, thiophene, thiosalcyclic acid, thiouracil,
and thiobendazole; aromatic essential oils such as oil of citron,
oil of cloves, oil of peppermint, sesamin, oil of wintergreen,
lemonene, pine oil, oil of eucalyptus, oil of sassifras, oil of
nutmeg, oil of mustard, oil of ginger, and citronella; water
insoluble amines such as aminoacetanilide, aminoacetophenone,
aminoacridine, aminoazotoluene, aminobenzenesulfonamide,
aminobenzathiazole, 2-amino- 1,2-diphenylethanol, aminosalicyclic
acid, and aminopterin; benzene and analine dyes such as
tetraazobenzene-beta-naphthol, acridine, dimethylaminoazobenzene,
anthracene, anthragallol, azobenzene, and 1,2-benzanthracene, and
antioxidants such as betahydroxyanisole and betahydroxytoluene.
In carrying out the method of the present invention, the internal
phase of an emulsion is first prepared in a polar solvent,
utilizing a surfactant which is soluble in the polar solvent in a
quantity of at least two parts by volume of the surfactant to one
part by volume of the unsaturated organic compound of the type
described above which is being emulsified. The surfactant used
should be one which is capable of forming a microemulsion. Those
skilled in the art will recognize that the following are known
requirements of a surfactant capable of forming a microemulsion: a
surfactant molecular chain length longer than the molecular chain
length of the compound being emulsified, solubility of the
surfactant in the compound being emulsified and vice versa, and an
adhesive attraction of the surfactant for the compound being
emulsified which is greater than the cohesive force between the
molecules of the compound. Because of the use of a polar organic
solvent and the desirability of a high aqueous dilution in the
final emulsion the surfactant also should have a
hydrophilic-lipophilic balance number of 11 or greater, and
preferably within the range of 11 to 14.
While the quantity of surfactant utilized is not critical within a
reasonable range, there should be a sufficient amount present in
the initial emulsion to assure surfacation of all of the micelles
upon division, and the quantity should not be so large as to result
in compaction and limit micelle division, or result in excess
surfactant being present in the external phase thus causing
possible phytotoxicity. It has been found that at least two parts
by volume of the surfactant to one part by volume of the compound
to be emulsified should be used and that in general quantities in
excess of a 4:1 ratio by volume should be avoided.
Examples of nonionic surfactants which can be utilized in the
invention include the polyoxyethylene sorbitan esters of mixed
fatty and resin acids as sold under the trademark "Atlox 8916T" by
Atlas Chemical Industries, Inc. of Wilmington, Delaware,
polysorbate 20 as sold under the trademark "Tween 20" by the Atlas
company, polyoxyethylene 20 sorbitan monopalmitate as sold under
the trademark "Tween 60" by the Atlas company, polyoxyethylene 20
sorbitan monooleate as sold under the trademark "Tween 80" by the
Atlas company, polyoxyethylene 40 stearate as sold under the
trademark "Myrj 52" by the Atlas company, polyoxyethylene 40
stearate as sold under the trademark "Myrj 525" by the Atlas
company, polyoxyethylene 50 stearate as sold under the trademark
"Myrj 53" by the Atlas company, polyoxyethylene esters of mixed
fatty and resin acids as sold under the trademark "Renex 20" by the
Atlas company, polyoxyethylene 20 palmitate as sold under the
trademark "G-2079" by the Atlas company, polyoxyethylene 23 lauryl
ether as sold under the trademark "Brij 35" by the Atlas company,
polyoxyethylene 20 cetyl ether as sold under the trademark "Brij
58" by the Atlas company, polyoxyethylene 20 oleyl ether as sold
under the trademark "Brij 98" by the Atlas company, polyoxyethylene
12 tridecyl ether as sold under the trademark "Renex 30" by the
Atlas company, polyoxyethylene 15 tridecyl ether as sold under the
trademark "Renex 31" by the Atlas company, polyoxyethylene 25
oxypropylene monostearate as sold under the trademark "G-2162" by
the Atlas company, and polyoxyethylene alkyl amine as sold under
the trademark "G-3780A" by the Atlas company.
Examples of anionic surfactants which can be utilized in the
invention include those sold under the trademarks "Triton X-151"
and "Triton X-152" by the Rohm & Haas Company of Philadelphia,
Pa., both of which are blends of alkylaryl polyethers, a blend of a
polyaryl polyether alcohol with an organic sulfonate such as sold
under the trademark "Triton X-172" by the Rohm & Haas Company,
a sodium salt of an alkylaryl polyether sulfonate such as sold
under the trademark "Triton X-200" by the Rohm & Haas company,
sodium salts of alkylaryl polyether sulfonates such as sold under
the trademarks "Triton W 30" and "Triton 770" by the Rohm &
Haas company, and a dioctyl sodium sulfosuccinate as sold under the
trademark "Triton Gr-5" by the Rohm & Haas company.
Examples of cationic surfactants which can be utilized in the
invention include the tertiary and quaternary water soluble amines,
stearyl dimethyl benzyl ammonium chloride, a trialkyl tin complex
having a high weight ratio of tertiary amine groups, benzalkonium
chloride, amido alkyl amine oxides, alkyl dimethylamine oxides, and
a hydrogenated tallow amine-steryl amine plus a vegetable amine as
sold under the trademark "Trymeen HTA 15". The amphoteric
surfactant sold under the trademark "Triton OS 15" by the Rohm
& Haas company, and which is a sodium salt of an alkylaryl
polyether sulfonate can also be utilized.
In general, it is preferable to use a nonionic or cationic
surfactant or a combination of a nonionic and an anionic. Because
of possible phytotoxicity, the concentration of anionic surfactant
should generally not exceed 20% by volume of the total quantity of
surfactant. The fact that an anionic surfactant carries a positive
ion, such as sodium, which is available for migration to the
micelle interface to increase the positive charge on the micelles,
makes it advantageous to use a small quantity of the anionic
surfactant in combination with a nonionic. The cationic surfactants
are used where additional protection from acid destruction is
desired. It is also known that some cationic surfactants are
germicidal compounds and these can be utilized to increase the
overall killing power of the microcolloidal emulsion when a
biologically active compound is being emulsified. The preferred
surfactant in all cases where it is compatible with the system is
Tween 80 as identified above. When it is desired to combine an
anionic surfactant with Tween 80, Triton X-151 is preferred.
Organic polar solvents which can be utilized in the invention
include the C.sub.8 and lower alcohols, dimethyl sulfoxide, diethyl
sulfoxide and methyl pyrrole. When it is desired to incorporate a
calcium chelating agent in the emulsion, as will be discussed in
greater detail hereinafter, dimethyl sulfoxide is very useful since
it can serve in the dual role of solvent and chelating agent. In
general, however, methyl alcohol is the preferred solvent because
of its lower cost. It may also be desirable in certain instances to
combine a relatively small volume of dimethyl sulfoxide with one of
the other polar solvents for optimum results.
The quantity of the solvent utilized is, of course, dependent upon
the concentration of the compound being emulsified. In order to
achieve a microcolloidal emulsion the unsaturated organic compound
should comprise no more than approximately 4% by volume of the
total emulsion with the polar solvent comprising from 10% to 25% of
the total volume. It is not essential that the resinous compound be
added to the internal phase, prepared as described above, at this
point in time but instead the resin can be added to the
microemulsion after dilution of the internal phase with water. It
is preferable, however, to add a first quantity of resin to the
internal phase prior to dilution with water and a second quantity
of either the same or a different resin to the initial gross
emulsion after the latter is formed. The resinous compound should
be characterized by a high number of positive ion accepting sites,
such as carboxyl (e.g. acrylic) or --CON-- (e.g. pyrrolidone)
groups, in each molecule of the compound. In addition to having a
high number of positive ion accepting sites which can react with a
positive ion donor, such as an acid or a base, to form a charged
resin molecule, the resinous compound should be water soluble.
Examples of resinous compounds which can be utilized in the present
invention include polyacrylic acid polymers, including ammoniacal
forms of the latter, carboxyvinyl polymers, pyrrolidone polymers,
and naturally occurring resinous compounds such as gum arabic,
agar-agar, and gum tragacanth. By a high number of positive ion
accepting sites is meant that the molecule should have at least as
many such sites as the naturally occurring resinous compounds
mentioned above and preferably at least one such site in each
repeating monomer of the molecule as in the case of polyacrylic
acid and pyrrolidone polymers.
The selection of the resinous compound is to be based upon the
charge assumed by the emulsion micelles. In some instances it is
found that the micelles assume an overall negative charge in which
case a resin having a carboxyl or equivalent group is utilized.
Upon addition of an equilibrating base or amine to an aqueous
solution of the resin, the resin molecule will assume an overall
negative charge and the liberated hydrogen and hydroxyl ions will
combine to form water. This charge will increase in magnitude as
equilibration continues and more of the monomer groups assume a
negative charge. This charge acts as a positive force charge (7a in
FIGS. 2 and 3) against the emulsion micelles and causes the latter
to divide, as previously explained. When a base is used in the
equilibration, the cation from the base forms a loose association
bond with the carboxyl group, giving the resin molecule an overall
negative charge, but also resulting in a partial positive charge on
the associated cation. The positive charge exerts a further
repulsive force (7b in FIGS. 2 and 3) against any cations which
have migrated to the micelle interphase, as previously explained.
This further enhances the pumping action of the resin.
When it is necessary that the resin assume an overall positive
charge, rather than a negative charge, a resinous compound having a
pyrrolidone or equivalent group is utilized. When an inorganic acid
is added to an aqueous solution of such a compound, the acid
hydrogen ion combines with the nitrogen of the pyrrolidone group to
give the resin an overall positive charge. This charge also
increases in magnitude as equilibration continues thereby effecting
micelle division.
The quantity of resin added at this point can vary over a
considerable range. It has been found, however, that the quantity
should generally not exceed approximately 0.1% by weight of the
final microemulsion since no further micelle division is observed
above this level. The optimum quantity is approximately 0.01% by
weight of the final microemulsion. Lesser quantities result in
larger micelle size in the final microemulsion with little effect
noted when the initial quantity of resin added is less than 0.005%
by weight of the final microemulsion.
To assure that the resinous compound goes into the solution of the
internal phase, it is desirable to partially equilibrate the resin
with either an acid or a base (depending upon whether the positive
ion accepting group is pyrrolidone or carboxyl) to adjust the pH
for maximum solution. For example, the polyacrylic acid resins are
partially equilibrated with NaOH to a pH of about 6.0 - 6.8 before
adding the resin to the emulsion. The pyrrolidone resins are pH
adjusted to about 8.0 before addition.
It is also desirable in many instances to incorporate in the
internal phase an antioxidant to prevent the formation of
peroxides. This is of value in preventing destruction of the
compound being emulsified, particularly where the compound is
biologically active and the microemulsion is placed in field use.
The antioxidant also prevents the formation of peroxides in certain
of the lower chain length vinyl and acrylic resins which could
otherwise cause further polymerization of the resin. The
antioxidant betahydroxytoluene is preferred with acrylictype resins
and the antioxidant betahydroxyanisole is preferred with
pyrrolidone-type resins. Examples of other antioxidants which can
be used in the invention include
N,N'-diphenyl-paraphenylonediamine, 2,2'-methylene/bis-(4
methyl-6-tertiarybutylphenol), N-phenyl-beta-naphthylamine,
4,4'-dimethoxydiphenylamine, parahydroxyanisole,
N-butyl-para-aminophenol, N,N'-di(secondary butyl)
para-phenylenediamine, hydroxyquinone, catechol, alphanaphthol, and
phenothiazine. The antioxidant should normally be present in a
ratio of at least one part antioxidant to 100 parts (by weight) of
the unsaturated organic compound being emulsified. The antioxidant
is preferably selected so that a microcolloidal emulsion of this
compound will also be formed.
After the internal phase of the yet to be formed emulsion is
completed by the addition of the unsaturated organic compound, the
antioxidant, the surfactant, and an initial quantity of resin to
the polar solvent, all as explained in detail above, the internal
phase is diluted to at least 70% by volume with water. Next, in
those cases where a microemulsion of an insecticide is being
prepared, it has been discovered that it is highly advantageous to
incorporate a calcium chelating agent in the emulsion. The presence
of calcium ions in the basil membrane of insects acts as a defense
mechanism to block the entry of any foreign molecules. By including
a calcium chelating agent, such as EDTA, in the emulsion of the
insecticide the calcium ions can be "tied up" and the emulsion
micelles are free to pass through the basil membrane of the
insect.
In general, coordination compounds of the bi-, tri-, hexa-, or
poly-dentate type such as diethylenetriamine and EDTA may be
utilized to sequester the calcium ions. Salts such as sodium
heparin and sodium citrate can also be used. As previously
mentioned, the solvent dimethyl sulfoxide can also serve as the
calcium chelator. EDTA is the preferred chelating agent and even
when DMSO is used as a solvent it is sometimes desirable to include
a quantity of EDTA. The quantity of EDTA or other chelating agent
added to the emulsion is not critical within a reasonable range
although it should generally comprise a quantity equal to at least
10% by weight of the quantity of unsaturated organic compound being
emulsified and not greater than 30% by weight of this compound. The
EDTA is normally dissolved in one ml of distilled and deionized
water before it is added to the emulsion.
At this point, an additional quantity of a resinous compound of the
type described above is added to the emulsion. This may be the same
resin as added prior to the formation of the initial emulsion or
another resin of the same type which will further enhance the
charge forces acting on the micelles after equilibration. The
quantity of resin added at this stage of the procedure can again
vary over a wide range. Most desirably, however, the quantity
should not exceed approximately 0.1% by weight of the final
microemulsion, since no benefits are obtained with higher levels,
and is preferably approximately 0.05% by weight of the final
microemulsion. In the event the resin addition prior to formation
of the initial gross emulsion is omitted, the quanity of resin
added at the present stage could exceed the optimum levels noted
above. Quantities less than the optimum result in larger micelle
size in the final microemulsion with little effect noted when this
second resin addition is in a quantity of less than 0.005% by
weight of the final microemulsion.
The resin present in the emulsion is now equilibrated using a
compound capable of donating positive ions to the positive ion
accepting sites of the resin to cause these sites to assume a
charge of the same sign as the sign of the charge on the micelles
of the initial gross emulsion. When the positive ion accepting site
is a carboxyl group, a strong base such as sodium hydroxide or
ammonium hydroxide, or an amine such as triethanolamine,
monoethanolamine, diisopropanolamine, dodecylamine, di(2-ethylhexyl
amine) or Ethomeen C25 (a product of Armour Industrial Chemical Co.
of Chicago, Ill.) is utilized in the equilibration. When the
positive ion accepting site is a pyrrolidone group, hydrochloric
acid should be utilized in the equilibration.
Sodium hydroxide is the preferred equilibrating medium for carboxyl
groups whenever the emulsion is at least 75% by volume water. In
the event that glycerol or ethylene glycol is added to the
emulsion, or a concentration of methyl alcohol of 25% or greater is
present, NH.sub.4 OH is the preferred equilibrating medium. For
systems using ethanol or isopropyl alcohol in concentrations of 10%
by volume or greater, an amine such as diisopropanolamine or
triethanolamine should be utilized for optimum results.
The quantity of the equilibrating medium added is calculated on the
basis of the quantity of resin utilized and how much of the
equilibrating compound will be needed to equilibrate a given
quantity of resin. The following are exemplary quantities in
milliliters of selected equilibrating compounds which would be
utilized to neutralize an emulsion containing 0.2% by weight of a
polyacrylic acid polymer of the type previously described:
__________________________________________________________________________
Final pH 10% 28% 50% 50% 50% after equilibration NaOH NH.sub.4 OH
D.I.P.A..sup.1 T.E.A..sup.2 M.E.A..sup.3
__________________________________________________________________________
4.0 0.21 0.10 0.2 0.3 0.04 4.5 0.45 0.16 0.5 0.6 0.11 5.0 0.83 0.24
0.8 0.9 0.23 5.5 1.13 0.36 1.2 1.4 .37 6.0 1.66 0.52 1.6 1.8 0.55
6.5 2.21 0.61 2.0 2.3 0.75 7.0 2.75 0.69 2.4 2.7 0.98 7.5 3,35 0.76
2.8 3.3 1.18 8.0 3.84 0.83 3.3 5.0 1.38 8.5 4.35 0.89 4.2 8.0 1.50
9.0 4.50 0.99 6.6 16.0 1.65
__________________________________________________________________________
.sup.1 D.I.P.A. diisopropylamine .sup.2 T.E.A. triethylamine .sup.3
M.E.A. monoethylamine
When the compound being emulsified is biologically active, such as
a pesticide, insecticide or fungicide, it is important that there
be no substantial change in the pH of the emulsion during the
equilibration. Any change greater than approximately 2 pH units
would be substantial and could result in denaturing of the
biologically active compound. The pH is maintained within a range
of 2 pH units by selecting the equilibrating compound so that the
equilibrating reaction does not release substantial quantities of
free H.sup.+ or OH.sup.- ions into the emulsion, and controlling
the quantity of the compound to avoid excess amounts which would
release excess quantities of H.sup.+ or OH.sup.- ions.
As a final step, the microemulsion is diluted with water to an
aqueous concentration of at least 95% by volume. While as
previously noted, the aqueous phase can comprise a smaller fraction
of the total emulsion, a 95% to 97% by volume aqueous phase is
preferred in most instances.
The following examples are indicative of the above-described
procedure. In each of the examples the compound being emulsified is
an insecticide, thus the optional step of adding a calcium
chelating agent is included in each procedure.
Example I
One gram (1.1 ml) of allethrin is dissolved in 10 ml of methyl
alcohol. To the resulting solution is added 0.01 gm of
betahydroxytoluene antioxidant.
Next, 2 ml of polysorbate 80 are added to the solution with gentle
mixing. A polyacrylic acid polymer such as that sold by the B. F.
Goodrich Chemical Co. of Cleveland, Ohio, under the trademark
"Good-rite WS 801", and having a molecular weight of 250,000, in a
quantity of 8 ml of a 1% by weight aqueous solution is equilibrated
to a pH of 6.8 using dilute NaOH and then added to the above
solution with gentle stirring.
The resulting internal phase for the microemulsion is then diluted
with sufficient water to provide a total volume of 80 ml of the
initial emulsion. A quantity of EDTA (0.1 gm) is dissolved in 1 ml
of distilled and deionized water which is then added to the
microemulsion. A total of 20 ml of a 0.5% by weight solution of
carboxypolymethylene, the pH of which has been adjusted to
approximately 6.0 by the addition of NaOH, is now added with
mixing. While mixing, the polyacrylic acid and carboxypolymethylene
are equilibrated by the addition of 15 ml of a 0.1% by weight
solution of sodium hydroxide. Finally, the equilibrated
microemulsion is diluted with water to a total of 1000 ml. The
above procedure can be repeated using similar quantities of any of
the exemplary compounds previously categorized as "oleoresinous and
natural carboxylic compounds."
Example II
One gram of chlorodane is dissolved in 20 ml of methyl alcohol. To
the resulting solution is added 0.1 gm of betahydroxytoluene. A
total of 3 ml of an alkylaryl polyether alcohol-sulfonate
surfactant, such as that sold under the trademark Triton X-151 by
the Rohm & Haas Co. of Philadelphia, Pa., is then added to the
solution.
Next, 8 ml of a 1% by weight aqueous solution of Good-rite WS 801
polyacrylic acid resin, which has been equilibrated to a pH of 6.8
as explained in Example I, is added with thorough mixing. Water is
added to bring the total volume up to 80 ml. EDTA (0.1 gm in 1 ml
of distilled and deionized water) is added to the resulting
emulsion with thorough mixing. An additional quantity of resin, 20
ml of a 0.5% by weight aqueous solution of carboxypolymethylene, is
now added.
The polyacrylic acid and carboxypolymethylene resins are now
equilibrated with 15 ml of a 0.1% solution of sodium hydroxide. The
equilibrated microemulsion is finally diluted to a volume of 1000
ml with water.
The foregoing procedure can be repeated utilizing similar
quantities of any of the exemplary compounds previously categorized
as "chlorinated hydrocarbons."
Example III
One gram of thymol is dissolved in 15 ml of methyl alcohol. As an
antioxidant, 0.01 gm of betahydroxyanisole is added to the
solution. A total of 2.0 ml of concentrated benzalkonium chloride
are now added to the solution with mixing.
Fifteen ml of a 1% aqueous solution of N-methyl-2-pyrrolidone
copolymer, which has been pH adjusted with NaOH to 8.0, is now
added to the solution. A sufficient quantity of water to provide a
total volume of 95 ml is then added to the previously prepared
internal phase. One-tenth gram of EDTA is now added to the
emulsion. A total of 5 ml of a 90% aqueous solution of
polyvinylpyrrolidone is added to supplement the methylpyrrolidone
previously added.
To equilibrate the pyrrolidone resins, 20 ml of a 0.1% by weight
solution of HCl is added until the final pH of the emulsion is
approximately 6.8. The equilibrated microemulsion is diluted with
water to a total volume of 1000 ml.
The foregoing procedure can be repeated using similar quantities of
any of the exemplary compounds previously categorized as "water
insoluble phenolics."
Example IV
Example III is repeated using 10 ml of dimethylsulfoxide as a
solvent for the thymol in place of the methyl alcohol. This allows
the EDTA to be omitted since the DMSO is itself a calcium chelating
agent.
Example V
One gram of 1-naphthyl N-methyl carbamate (available under the
trademark "Sevin" from the Union Carbide Corporation of New York,
N.Y.) is dissolved in 30 ml of methyl alcohol and 0.01 gm of
betahydroxytoluene is added to the solution. A total of 3 ml of
polysorbate 60 is then added to the solution to complete the
internal emulsion phase.
A polyacrylic acid polymer of the same type as utilized in Example
I and similarly adjusted in pH is utilized to form a 1% by weight
aqueous resin solution. Eight ml of this resin solution are added
to the internal phase referred to above subsequent to which
sufficient water is added to bring the total volume to 80 ml and
form the aqueous emulsion. EDTA (0.1 gm) is now added to the
emulsion menstruum.
Next, a second quantity of resin, 20 ml of a 0.5% by weight aqueous
solution of carboxypolymethylene which has been pH adjusted to
approximately 6.0 is added to the emulsion with mixing.
Equilibration is achieved with the addition of 15 ml of a 0.1% by
weight solution of NaOH. Finally, the emulsion is diluted to a
total volume of 1000 ml with water.
The foregoing procedure can be repeated using similar quantities of
any of the exemplary compounds previously categorized as "carbamate
compounds."
Example VI
To one gram of 8-hydroxyquinoline, a total of 3.3 ml of a blend of
polysorbate 80 (3.0 ml) and the anionic surfactant identified in
Example II as being sold under the trademark Triton X-151 (0.3 ml),
plus 25 ml of methyl alcohol are added simultaneously. It is highly
desirable to dissolve the hydrocarbon in the surfactant and the
solvent simultaneously for optimum results. To the resulting
solution is added 0.03 gm of betahydroxytoluene.
Next, a polyacrylic acid polymer of the type identified in Example
I and pH adjusted as described in the latter example, is added to
the solution in a quantity of 7 ml of a 1% aqueous solution after
which water is added to bring the total volume to 80 ml and form
the emulsion. The calcium chelating agent EDTA (0.1 gm) is now
added to the emulsion.
A second quantity of resin, 20 ml of a 0.5% by weight aqueous
solution of carboxypolymethylene, which has been pH adjusted to
approximately 6.0 with NaOH, is added to the emulsion menstruum
with thorough mixing. Equilibration is achieved with 25 ml of 0.1%
by weight solution of NaOH. Finally, sufficient water is added to
bring the total volume to 1000 ml.
The foregoing procedure can be repeated using similar quantities of
any of the exemplary compounds previously categorized as "quinonine
and quinoline type compounds."
Example VII
To one gram of Sudan Red dye, which is available from the General
Aniline & Film Corporation of New York, N.Y., is added 30 ml of
methyl alcohol to achieve solution. Betahydroxytoluene is then
added to the resulting solution in a quantity of 0.02 gm.
Next 5 ml of polysorbate 80 are added with mixing. Ten ml of a 1%
by weight aqueous solution of the polyacrylic acid polymer
Good-rite WS 801, as identified in Example I, which has been pH
adjusted to 6.8 as explained in the referenced example, is added to
the solution.
Water is added to the above-prepared internal phase to bring the
total volume to 85 ml and form the initial emulsion. EDTA, prepared
according to Example I, is added in a quantity of 1 ml. Fifteen ml
of an aqueous solution of carboxypolymethylene (containing 0.075 gm
of the resin) is then added. Eleven ml of a 1% by weight solution
of NaOH is utilized to equilibrate the resin with the final pH of
the emulsion being 7.5. The final equilibrated emulsion is diluted
with water to a volume of 1000 ml.
Ethyl alcohol can be substituted for methyl alcohol in the above
procedure with equally satisfactory results. The procedure can also
be repeated using similar quantities of any of the exemplary
compounds previously categorized as "benzene and analine dyes."
Example VIII
One gram of oil of cloves is dissolved in ethyl alcohol by adding
the latter to the former. Betahydroxytoluene (0.01 gm) is added to
the resulting solution. Six ml of polysorbate 60 are then
added.
The polyacrylic acid polymer Good-rite WS 801, as identified in
Example I, is added in a quantity of 4 ml after pH adjustment to
6.8. Water is added next to bring the total volume to 80 ml. One ml
of EDTA, prepared as explained in Example I is then added to the
microemulsion. Twenty ml of an aqueous solution of
carboxypolymethylene (containing 0.1 gm of the resin) are added and
equilibration is achieved with 15 ml of a 0.1% by weight aqueous
solution of NaOH. Final dilution to 1000 ml is achieved by adding
water.
The above procedure can be repeated using similar quantities of any
of the exemplary "essential oils" previously mentioned.
Example IX
One gram of thiabendazole is dissolved in 10 ml of methyl pyrrole.
Betahydroxyanisole (0.01 gm) is added to the resulting solution.
Next, 3 ml of concentrated benzalkonium chloride are added with
mixing.
To the above solution of the internal phase, 12 ml of a 1% aqueous
solution of methyl pyrrolidone, which has been pH adjusted to 8.0
with hydrochloric acid, are added. Dilution to 80 ml with water
forms the initial emulsion, and 1.0 ml of a 0.1 gm aqueous solution
(distilled and deionized water) of EDTA is added as a calcium
chelating agent.
Next, 20 ml of polyvinylpyrrolidone (90% by weight aqueous
solution) is added and the resin is equilibrated with 20 ml of a
0.4% by weight solution of HCl. The resulting microemulsion is
diluted to a total volume of 1000 ml with water.
The above procedure can be repeated using similar quantities of any
of the exemplary "thiol type compounds" previously mentioned.
Example X
One gram of aminoacridine is added to 25 ml of isopropyl alcohol
with 0.01 gm of betahydroxytoluene present as an antioxidant. Four
ml of polysorbate 60 are then added to complete the internal phase
of the emulsion.
The polyacrylic acid polymer Good-rite WS 801 as identified in
Example I (pH equilibrated to 6.8) is then added in a quantity of 6
ml. Water is added to a total of 80 ml to form the initial
emulsion. EDTA, in a quantity of 0.3 gm in 1 ml of distilled and
deionized water is added next. A solution of 0.1 gm of
carboxypolymethylene in 20 of water (pH 6.0) is incorporated into
the emulsion as an additional resin pumping agent.
The resins are equilibrated with 25 ml of a 0.1% by weight solution
of NH.sub.4 OH. The final pH is 8.0. After equilibration, the
resulting microemulsion is diluted to a total volume of 1000 ml
with water.
The above procedure can be repeated using similar quantities of any
of the exemplary compounds previously categorized as "water
insoluble amines."
Example XI
Mercuric resourcinol acetate, 1 gm, is dissolved in 5 ml of methyl
pyrrole with 0.01 gm of betahydroxyanisole being added as an
antioxidant. To the resulting solution, 4 ml of concentrated
benzalkonium chloride is added.
Methyl pyrrolidone is the resin pumping agent utilized and 15 ml of
a 1% by weight aqueous solution of pH=80 incorporated in the
solution of the internal phase. Water is added to bring the total
volume to 95 ml. EDTA, 0.2 gm dissolved in 2 ml of distilled and
deionized water, is added to the resulting emulsion as is
polyvinylpyrrolidone in a quantity of 5 ml of a 90% by weight
aqueous solution. The resins are equilibrated with 20 ml of a 0.1%
by weight solution of HCl. Finally, the microemulsion is diluted to
a total volume of 1000 ml with water.
The following tests were run to determine the micelle size of the
microcolloidal emulsions prepared according to the teachings of the
present invention. In each case the optical refraction (O.R.) was
measured using photomultiplier cells, a preamplifier unit, and
registered on a standard millivolt meter. Five ml standard quartz
cuvettes were used as emulsion receptacles during the optical
measurements.
First of all, emulsions of ten different unsaturated organic
compounds were prepared without the addition of the resinous
compound and equilibration of the latter with an acid or a base
(see Examples XII - XVI, infra). The resulting emulsions were clear
although they were found to reflect a Tyndell beam in the visible
light range as reported in Table 1 below.
Table 1 ______________________________________ Optical Refracton
(Visible Spectrum) of Microemulsions Prepared Without Utilization
of Resin Pumping Principle O.R. (%) O.R. (%) Emulsion 1:100
dilution 1:1000 dilution ______________________________________ 1.
Pyrethrin 2.0 0.2 2. Allethrin 3.3 0.3 3. Sevin 2.7 0.25 4.
8-hydroxyquinoline 3.4 0.36 5. Juglone 3.2 0.29 6. Perthane 3.7
0.33 7. Rhothene 3.6 0.34 8. Sudan Red 1.8 0.14 9. Clove Oil 5.2
0.46 10. Oil of Wintergreen 4.2 0.39
______________________________________
The results reported in Table 2 below indicate the effects of the
resin pumping action on the micelle size and the ability of
micelles to reflect light.
Table 2
__________________________________________________________________________
Optical Refraction (Visible Spectrum) of Microemulsions Prepared
Utilizing Resin Pumping Action O.R. (%) Before O.R. (%) Before O.R.
(%) After Equilibration Equilibration Equilibration Emulsion 1:100
dilution 1:1000 Dilution 1:100 Dilution
__________________________________________________________________________
1. Pyrethrin 2.36 .55 .35 2. Allethrin 3.54 .65 .37 3. Sevin 3.05
.60 .42 4. 8-hydroxy- 3.78 .72 .33 quinoline 5. Juglone 3.57 .60
.35 6. Perthane 4.05 .63 .36 7. Rhothane 4.0 .69 .33 8. Sudan Red
2.2 .50 .34 9. Clove Oil 5.55 .80 .32 10. Oil of Winter- 4.60 .85
.35 green O.R. (%) After Calculaed* O.R. (%) Equilibration
Attributable to Resin 1:1000 Dilution Alone (1:100 dilution)
__________________________________________________________________________
1. .35 .36 2. .37 .24 3. .43 .35 4. .34 .38 5. .36 .37 6. .35 .35
7. .34 .40 8. .35 .40 9. .35 .35 10. .34 .40
__________________________________________________________________________
*column 1, Table 2 less column 1, Table 1
As indicated above, the optical refraction of each emulsion dropped
back to the value expected for the resin alone after equilibration.
To confirm that all of the refraction indicated in columns three
and four in fact was attributable to the resin itself, to each of
the emulsions was added 1% by weight of NaCl. This caused
precipitation of the resin. Following centrifugation and decanting
of the supernatant fractions from each emulsion, the supernatants
were again tested for optical refraction and all values found to be
zero when corrected against a water blank. To prove the presence of
the emulsion micelles, each of the samples from which the resin had
been precipitated was tested against a standard U.V. light source
(Blak-Ray UVL-21, 115 v, 60 cycle, 0.12 amps) and found in every
case to exhibit some refraction.
To determine the stability of the microemulsions prepared according
to the method of the present invention, four different compounds
were prepared utilizing 0.1% by weight active ingredient in a total
emulsion volume of 1000 ml. The percentage of effectivity lost is
based upon spectroscopic examination in the ultraviolet as well as
insect minometer tests for potency. As indicated in the following
table the microcolloidal emulsions (MCE) prepared according to the
invention were much more stable than ordinary emulsions.
Table 3
__________________________________________________________________________
Percent Effectivity Lost After One Month Rm. Temp. 120.degree.F.
Active MCE Ordinary MCE Ordinary Ingredient Rm. Temp. Emulsion
(Std.) 120.degree. F. Emulsion (Std.)
__________________________________________________________________________
Pyrethrin 6 58 12 78 Allethrin 8 63 15 86 Sevin 14 97 22 100 Oil of
Cloves 5 30 6 70
__________________________________________________________________________
Tests run to determine the extent of permeability in insects of
microcolloidal emulsions prepared according to the method of the
present invention were also run. A 0.01% by weight aqueous
microemulsion of pyrethrin was prepared according to the method of
the present invention and an ordinary emulsion of the same compound
at the same strength was also prepared. A second control was
prepared using an ordinary emulsion plus dimethyl sulfoxide (DMSO)
in a 10% by weight concentration. As those skilled in the art will
appreciate, DMSO is generally regarded as the most highly
penetrable solvent known. Grasshoppers (15 for each group) were
chosen for this penetrability test. All insects tested were dipped
in the respective emulsions for three seconds duration and then
allowed to stand for three hours to permit the chemical to
penetrate the exoskeleton. The chitinous exoskeleton was then
removed to expose the underlying membrane and dipped in a 4%
solution of NaOH. The purple Formazan that results is an indication
of the pyrethrin concentration in the membrane. The purple Formazan
pyrethrin alkylate is extracted from the tissue by placing the
latter in test tubes containing 75% isopropyl alcohol and 25%
glycerol with heating to a gentle boil. The extract was then placed
in a photometer and the optical density (O.D.) read.
The results were compared against the standard prepared by killing
an insect, removing the exoskeleton, dipping the basil membrane
into an ordinary emulsion of pyrethrin and extracting the pyrethrin
to obtain the purple Formazan sample which was placed in the
photometer and given a value of 4.sup.+. The results are stated in
Table 4 below.
Table 4
__________________________________________________________________________
Purple Formazan Test of Insect Penetrability (4+= optimum O.D.
value) Control Emul- Microcolloidal Emul- Control Emulsion sion
Pyrethrin Insect No. sion - Pyrethrin O.D. Pyrethrin O.D. plus DMSO
O.D.
__________________________________________________________________________
1 2+ trace 1+ 2 1+ trace 2+ 3 2+ neg. 1+ 4 2+ neg. 1+ 5 2+ trace
trace 6 1+ neg. 1+ 7 trace neg. trace 8 1+ trace 2+ 9 2+ 1+ 1+ 10
2+ trace trace 11 3+ neg. 1+ 12 1+ neg. trace 13 trace trace trace
14 2+ trace 1+ 15 2+ trace trace Average 1+ - 2+ neg. - trace 1+
__________________________________________________________________________
From the data tabulated above it is apparent that the microemulsion
prepared according to the present invention gave far better
penetration than either the ordinary emulsion or the emulsion plus
the solvent dimethyl sulfoxide.
To determine the penetrability of emulsions prepared according to
the present invention through wood, the following test was run. A
0.01% by weight aqueous microemulsion of allethrin and a 0.01% by
weight aqueous microemulsion of Sudan Red dye were prepared
according to the present invention. Similar quantities of the
allethrin and dye were dissolved in the following solvents: ether,
methyl alcohol, chloroform, terpentine, benzene and dimethyl
sulfoxide (DMSO).
One ml of each solution or emulsion was injected into a block of
live wood approximately 1 inch thick and 5 inches - 7 inches in
diameter and allowed to penetrate for one hour. A value of 4+ was
given to the maximum area penetrated and a value of 3+ as given for
penetration of an area three-fourths as large as the maximum area,
and so on. The results are tabulated in Table 5 below.
Table 5
__________________________________________________________________________
Wood Block Penetration 4+= maximum area penetrated Column A =
allethrin Column B = Sudan Red dye tr. = trace neg. = negative
penetration Ordinary Micro- Chloro- Emulsion emulsion Ether
CH.sub.3 OH form Terpentine Block A B A B A B A B A B A B
__________________________________________________________________________
1 neg. neg. 4+ 3+ 1+ 1+ tr. tr. tr. tr. neg. neg. 2 neg. neg. 3+ 4+
1+ tr. tr. 1+ neg. tr. neg. neg. 3 neg. neg. 4+ 4+ 1+ 1+ tr. tr.
neg. tr. neg. neg. 4 neg. neg. 4+ 4+ tr. 1+ tr. tr. neg. tr. neg.
neg. 5 neg. neg. 4+ 3+ 1+ tr. tr. 1+ tr. 1+ neg. neg. 6 neg. neg.
4+ 4+ 1+ 1+ tr. tr. neg. tr. neg. neg. 7 neg. neg. 3+ 4+ 1+ 1+ tr.
1+ neg. tr. neg. neg. 8 neg. neg. 4+ 4+ 2+ 1+ tr. 1+ neg. 1+ neg.
neg. 9 neg. neg. 4+ 4+ 1+ 1+ tr. tr. tr. tr. neg. neg. 10 neg. neg.
4+ 4+ 1+ 1+ tr. tr. neg. tr. neg. neg. Block Benzene DMSO A B A B
__________________________________________________________________________
1 tr. tr. 2+ 1+ 2 tr. 1+ 1+ 1+ 3 tr. 1+ 1+ 1+ 4 tr. tr. 1+ 1+ 5 tr.
1+ 2+ 1+ 6 tr. 1+ 1+ 1+ 7 tr. 1+ tr. tr. 8 tr. 1+ 1+ tr. 9 tr. 1+
1+ 1+ 10 tr. tr. 2+ 1+
__________________________________________________________________________
Actual insect kill tests were run to compare the killing
effectiveness of microcolloidal emulsions (MCE) of insecticidal
compounds prepared according to the invention with ordinary
emulsions (control) of the same compound. The chemicals Sevin,
allethrin, and pyrethrin were tested and in each case a
microemulsion was prepared according to the procedures set forth in
Examples V, I and I, respectively. The control emulsions were
prepared using the similar quantities of the compounds. In each
case readings were taken at the end of the first, second, fifth and
twenty-fourth hours and in determining the experimental values for
L.D..sub.50 corrections were made for any shifts in viability of
the insects that occurred after the initial readings. The results
are summarized in Tables 6 - 11.
Table 6 ______________________________________ Effectivity of Sevin
on hymenoptera (Yellow Jacket Hornet) Total No. Total No. % Viable
Dilution Insects (MCE) Insects (Control) 24 Hrs. (MCE)
______________________________________ 1:1000 10 10 0 1:4000 10 10
0 1:10000 10 10 20 1:20000 10 10 90 1:40000 10 10 100 1:60000 10 10
100 % Lethal % Viable % Lethal Dilution 24 Hrs. (MCE) 24 Hrs.
(Control) 24 Hrs. (Control) ______________________________________
1:1000 100 80 20 1:4000 100 100 0 1:10000 80 100 0 1:20000 10 100 0
1:40000 0 -- -- 1:60000 0 -- --
______________________________________ LD.sub.50 experimental for
Sevin MCE = 1:15000 dilution LD.sub.50 experimental for Sevin
control = 1:500 dilution (approx.)
The above test with Sevin was repeated using orthoptera (German
cockroach), diptera (housefly) and coleoaptera (mealy worm beetle
larva). The dilution values found for both the MCE and the control
emulsion are given in Table 7.
Table 7 ______________________________________ Effectivity of Sevin
on Selected Insects - LD.sub.50 Dilution Ratio LD.sub.50 LD.sub.50
Insect MCE Control ______________________________________
Orthoptera 1:35000 1:2500 Diptera 1:17500 1:2500 Coleoaptera
1:70000 1:3250 ______________________________________
Table 8 ______________________________________ Effectivity of
D-Trans Allethrin on Orthoptera (German Cockroach) Total No. Total
No. % Viable Dilution Insects (MCE) Insects (Control) 24 Hrs. (MCE)
______________________________________ 1:1000 50 50 0 1:4000 50 50
0 1:10000 50 50 0 1:20000 50 50 34 1:40000 50 50 94 1:60000 50 50
93 % Lethal % Viable % Lethal Dilution 24 Hrs. (MCE) 24 Hrs.
(Control) 24 Hrs. (Control) ______________________________________
1:1000 100 0 100 1:4000 100 96 4 1:10000 100 100 0 1:20000 66 100 0
1:40000 6 100 0 1:60000 2 100 0
______________________________________ LD.sub.50 experimental for
Allethrin MCE 1:24,500 dilution LD.sub.50 experimental for
Allethrin Control 1:2500 dilution
The above test with allethrin was repeated using hymenoptera
(yellow jacket hornet), diptera (housefly), and coleoptera (mealy
worm beetle larva). The dilution values found for both the MCE and
the control emulsion are tabulated below.
Table 9 ______________________________________ Effectivity of
Allethrin on Selected Insects - LD.sub.50 Dilution Ratio LD.sub.50
LD.sub.50 Insect MCE Control ______________________________________
Hymenoptera 1:17500 1:650 Diptera 1:50000 1:4750 Coleoptera 1:17500
1:2500 ______________________________________
Table 10 ______________________________________ Effectivity of
Pyrethrin on Diptera (Housefly) Total No. Total No. % Viable
Dilution Insects (MCE) Insects (Control) 24 Hrs. (MCE)
______________________________________ 1:1000 50 50 0 1:4000 50 50
0 1:10000 50 50 0 1:20000 50 50 0 1:40000 50 50 0 1:60000 50 50 0 %
Lethal % Viable % Lethal Dilution 24 Hrs. (MCE) 24 Hrs. (Control)
24 Hrs. (Control) ______________________________________ 1:1000 100
0 100 1:4000 100 68 32 1:10000 100 96 4 1:20000 100 100 0 1:40000
100 100 0 1:60000 100 100 0 ______________________________________
LD.sub.50 experimental for Pyrethrin MCE = could not be calculated
although greater than 1:60000 LD.sub.50 experimental for Pyrethrin
Control = 1:2750
The above test with pyrethrin was repeated using hymenoptera
(yellow jacket hornet), orthoptera (German cockroach) and
coleoptera (mealy worm beetle larva). The dilution values found for
both the MCE and the control emulsion are tabulated below.
Table 11 ______________________________________ Effectivity of
Pyrethrin on Selected Insects - LD.sub.50 Dilution Ratio LD.sub.50
LD.sub.50 Insect MCE Control ______________________________________
Hymenoptera 1:16500 1:1750 Orthoptera 1:50000 1:2750 Coleoptera
1:25000 1:2500 ______________________________________
From the data in Tables 6 through 11 it is apparent that the kill
effectivity of microcolloidal emulsions prepared according to the
present invention far exceeds that of conventional emulsions. In
every case, the dilution ratio for the MCE is much higher than for
the control.
Tests were also run to determine whether or not the increased
efficacy of biologically active compounds, such as insecticides,
prepared as microemulsions according to the present invention, is
accompanied by an increase in mammalian toxicity.
The known toxic level for both Sevin and allethrin insecticides is
between 0.5 and 1.5 gm/kg of body weight. In a 1:1000 dilution
emulsion (0.1% by weight active ingredient) three gallons of the
emulsion would be required to provide the MLD. Based on the fact
that an insecticide prepared as a microemulsion would normally be
diluted at from 1:10000 -- 1:20000, and the fact that a dog could
not conceivably consume even three gallons of an insecticide, one
quart of the 1:1000 emulsion was selected for the toxicity tests.
This volume of insecticide is the maximum feasible which a dog
could contact since it is the amount which adheres to a dog when it
is completely immersed in the emulsion. It is to be understood,
however, that the actual quantity of the active ingredient could
normally not be expected to exceed from one-tenth to one-twentieth
of the quantity applied in the 1:1000 test dilution, even if the
animal were completely immersed.
Fifteen test dogs and fifteen control dogs were completely immersed
in 0.1% by weight aqueous emulsions of allethrin. One emulsion was
prepared according to the invention (test) and the other was an
ordinary emulsion (control). The dogs in each group were observed
for general appearance, grooming habits, sneezing or coughing,
feeding habits and intake, appearance of feces, appearance of eyes
and mucus membranes, nervousness, measured water intake,
urinalysis, white and red blood counts. Except for the fact that
two animals in the control group contacted pneumonia, which was
cleared up with medication, all animals in both groups were normal
in every respect after some initial excitement and generally poor
appearance from the dunking.
The same test was repeated using 15 test animals and 15 control
animals with 0.1% emulsions of the insecticide Sevin being utilized
in place of allethrin with similar results.
To further confirm that the biologically active microcolloidal
emulsions of the invention do not result in increased mammalian
toxicity tests were run on mice given intraperitoneal injections of
emulsions containing insecticidal compounds. The average weight of
some 240 mice used as a test group and another 240 mice used as a
control group was 20 gm. Using the known value for the toxicology
of allethrin of 0.5 - 1.5 gm/kg of body weight, the calculated
lethal dose for a 20 gm mouse, utilizing a 1% aqueous emulsion,
would be from 1 to 3 gm.
Twelve groups of 20 mice each (20 test mice plus 20 control mice)
were injected intraperitoneally with varying amounts of 1% aqueous
emulsions of pyrethrin. The test groups were injected with a
microemulsion prepared according to the present invention and the
control groups were injected with an ordinary emulsion.
Table 12 ______________________________________ Toxicity to Mice of
Ordinary Emulsion (Control) and Microcolloidal Emulsion (MCE) of
Sevin Injected Intraperitoneally No. Animals No. Animals Group No.
Dosage (gm) MCE Control (20 animals each) I.P. Injection Viable
Dead Viable Dead ______________________________________ 1 3 0 20 0
20 2 2 3 17 4 16 3 1 12 8 11 9 4 0.9 18 2 17 3 5 0.8 20 0 19 1 6
0.7 19 1 20 0 7 0.6 20 0 20 0 8 0.5 20 0 20 0 9 0.4 20 0 20 0 10
0.3 20 0 20 0 11 0.2 20 0 20 0 12 0.1 20 0 20 0
______________________________________ LD.sub.50 experimental for
MCE = 1+ gm dosage LD.sub.50 experimental for Control = 1+ gm
dosage MLD experimental for MCE = 0.7 gm dosage MLD experimental
for Control = 0.8 gm dosage
When the above test was repeated substituting 1% aqueous
microcolloidal and ordinary emulsions of allethrin for the Sevin
the results summarized below were observed:
Ld.sub.50 experimental for MCE = 1+ gm dosage
Ld.sub.50 experimental for Control = 1+ gm dosage
Mld experimental for MCE = 0.7 gm dosage
Mld experimental for Control = 0.8 gm dosage
Thus in both instances the values for the LD.sub.50 and the MLD of
the microemulsion and the ordinary emulsion were essentially the
same and within known toxic levels for these chemicals. There is,
therefore, no increased toxicity to mammals from the microcolloidal
emulsions of the invention and the increased efficacy of the
emulsified compound is clearly specific for the insects, fungi,
etc, which it is desired to kill.
As indicated by the data in the above tables, when the method of
the present invention is employed with biologically active
compounds, such as insecticides, the efficacy of the compound can
be greatly increased without an increase in mammilian toxicity. The
increased efficacy is attributable to smaller emulsion micelle
size, greater penetrability, increased stability, greater
specificity as a result of protection from reaction with the
environment, and greater adhesion to both the plants protected and
the insects to be killed. It will thus be appreciated that
incorporation of the resinous compound into the emulsion serves not
only as an effective "pumping agent" to reduce micelle size, but
when the emulsion is applied to a plant or other living body and
the aqueous phase evaporates, the resin is left as a protective
shield for the micelles. The increased effectiveness allows for
smaller quantities of the active compound and its organic solvent
to be utilized while also making available many relatively "safe"
compounds heretofore having found only limited use because of their
low kill effectivity. The method of the invention also makes
economically feasible the extraction of many useful compounds with
relatively harmless solvents such as alcohol, because of the
substantially lower quantity of the compounds which need be
used.
The method of the present invention can also be used to protect cut
wood from deterioration in general and from insects by using an
emulsion of a protective compound to saturate the wood. Because of
the increased effectiveness and penetrability of any active
compound microcolloidalized by the inventive process, superior
results are obtained with smaller quantities of the compound. The
method of the invention can also be employed with water soluble
dyes to impart color to wood and wood products. Still another use
of the invention method is in the inoculation of animals by
applying microcolloidal emulsion to the skin rather than by
injection.
ALTERNATIVE FORM OF THE INVENTION
In those cases where the resinous covering which protects the
emulsion micelles is either undesirable or unnecessary, the
efficacy of an unsaturated organic compound of the type described
on page 12 and having biological activity can be greatly increased
utilizing the following method. Examples of compounds which can be
utilized in this alternative procedure include all of those
compounds listed on pages 13 and 14 which are biologically active
as insecticides, fungicides, etc.
In carrying out this alternative method, the internal phase of an
emulsion is first prepared in a polar solvent, utilizing a
surfactant which is soluble in the polar solvent in a quantity of
at least eight parts by volume of the surfactant to one part by
volume of the unsaturated organic compound. The surfactant should
again be one capable of forming a microemulsion as discussed
previously in conjunction with the preferred embodiment of the
invention. The various surfactants previously listed as exemplary
and set forth on page 15 can be utilized in this alternative
procedure. Examples of polar solvents which can be utilized include
those previously listed on page 17.
As with the procedure previously described, it is preferable to
incorporate an antioxidant into the internal phase to guard against
oxidation of the biologically active compound. Examples of
antioxidants which can be utilized include those listed on page 20.
the antioxidant should normally be present in a ratio of at least
one part antioxidant to 100 parts (by weight) of the compound being
emulsified.
After the internal phase of the yet to be formed emulsion is
completed by the addition of the unsaturated organic compound, the
antioxidant, and the surfactants, as explained above, the internal
phase is diluted to at least 70% by volume with water. The
resulting emulsion is characterized by emulsion micelles of a
reduced size although the micelles do show some reflection of light
in the visible spectrum.
To "tie up" the calcium ions in the basil membrane of an insect, a
chelating agent is added to the emulsion at this stage. EDTA is the
preferred chelating agent, although other known calcium chelators,
including those specified on page 21 can be utilized. The quantity
of the chelating agent utilized should be at least 10% and not
greater than 30% by weight of the quantity of the compound being
emulsified.
As a final step, the emulsion prepared as set forth above is
preferably diluted to at least 95% by volume water. While as
previously noted, the aqueous phase may comprise as little as 70%
by volume water, in most cases a more dilute emulsion is
desirable.
While an emulsion prepared by the alternative method described
above is not as stable against acid, alkali and heat deterioration
because of the absence of the protective resin, it has been found
that such an emulsion exhibits superior penetrability approaching
that reported in Tables 4 and 5, infra. Efficacy of the emulsions
prepared according to this alternative procedure has also been
found to be greatly superior to ordinary emulsions and approaches
that reported in Tables 6 - 11. This alternative method of
preparing an emulsion of a biologically active compound is
particularly adapted for use where the emulsion is intended to be
used as an injection systemic for protection of large plants such
as trees.
The example set forth below are indicative of the procedure to be
followed when practicing the alternative form of the invention
described above.
Example XII
One gram (1.1 ml) of pyrethrin is dissolved in 10 ml of methyl
alcohol. To the resulting solution is added 0.01 gm of
betahydroxytoluene antioxidant.
Next, 8 ml of polysorbate 80 are added to the solution with gentle
mixing. The resulting internal phase is then diluted with water to
form the emulsion with the quantity of water added being sufficient
to provide a total volume of 80 ml. One-tenth gram of EDTA
dissolved in 1 ml of distilled and deionized water is then added to
the emulsion. Finally, the emulsion is diluted with water to a
total volume of 1000 ml.
The above procedure can be repeated using similar quantities of any
of the exemplary compounds previously categorized as "oleoresinous
and natural carboxylic compounds."
Example XIII
One gram of the insecticide sold under the name "Perthane" (100%)
by the Rohm & Haas Co. of Philadelphia, Pennsylvania and based
on 1,1-dichloro-2,2-bis(para-ethylphenyl)-ethane is dissolved in 20
ml of methyl alcohol. To the resulting solution is added 0.1 gm of
betahydroxytoluene. A total of 10 ml of an alkylarly polyether
alcohol-sulfonate surfactant, such as that sold under the trademark
Triton X-151 by the Rohm & Haas Co. of Philadelphia,
Pennsylvania is then added to the solution.
Water is added to bring the total volume to 80 ml and form the
emulsion. EDTA (0.1 gm in 1 ml of distilled and deionized water) is
added resulting the reeulting emulsion with thorough mixing.
Finally, the emulsion is diluted to a total volume of 1000 ml with
water.
The foregoing procedure can be repeated utilizing similar
quantities of any of the exemplary compounds previously categorized
as "chlorinated hydrocarbons."
Example XIV
One gram of methylated resorcinol is dissolved in 15 ml of methyl
alcohol. As an antioxidant, 0.01 gm of betahydroxyanisole is added
to the solution. A total of 8.0 ml of concentrated benzalkonium
chloride are now added to the solution with mixing.
Next, a sufficient quantity of water to provide a total volume of
95 ml is added to form the emulsion and one-tenth gram of EDTA is
introduced. Finally, the emulsion is diluted to a total volume of
1000 ml with water.
The foregoing procedure can be repeated using similar quantities of
any of the exemplary compounds previously categorized as "water
insoluble phenolics."
Example XV
One gram of chlorophenyl carbamate is dissolved in 30 ml of methyl
alcohol and 0.01 gm of betahydroxytoluene. A total of 10 ml of
polysorbate 60 is then added to the solution to complete the
internal emulsion phase. Next, sufficient water is added to bring
the total volume to 80 ml and form the aqueous emulsion. The
calcium chelating agent EDTA (0.1 gm) is introduced into the
emulsion menstruum and as a final step the emulsion is diluted to a
volume of 1000 ml with water.
The foregoing procedure can be repeated using similar quantities of
any of the exemplary compounds previously categorized as "carbamate
compounds."
Example XVI
To one gram of 8-hydroxyquinoline a total of 11 ml of a blend of
polysorbate 80 (10 ml) and the anionic surfactant identified in
Example II as being sold under the trademark Triton X-151 (1.0 ml)
plus 25 ml of methyl alcohol are added simultaneously. It is highly
desirable to dissolve the hydrocarbon in the surfactant and the
solvent simultaneously for optimum results. To the resulting
solution is added 0.03 gm of betahydroxytoluene.
To form the emulsion, water is added to bring the total volume to
80 ml and 0.1 gm of EDTA is included in the emulsion. Finally,
sufficient water is added to bring the total water to 1000 ml.
The foregoing procedure can be repeated using similar quantities of
any of the exemplary compounds previously categorized as "qunionine
and quinoline type compounds."
SECOND ALTERNATIVE FORM OF THE INVENTION
It has also been discovered that polyacrylic acid polymers can be
utilized to form highly stable pastes and powders of biologically
active unsaturated organic compounds of the type previously
described. The following described procedure is particularly
adapted for use with those compounds which are commonly sold in
powder or paste form and for which a ready market as a dilute
aqueous emulsion does not exist. Surface active properties are
imparted to a polyacrylic acid polymer by dual neutralization
allowing the polymer to act as an emulsifier and stabilizer.
An aqueous solution of a polyacrylic acid polymer, is first
prepared, preferably utilizing from 0.1 to 0.3% by weight of the
polymer. The polymer is then partially equilibrated with an
appropriate base, such as NaOH or NH.sub.4 OH, with the carboxyl
groups of the polymer reacting with the base to form water and
yield a substituted polymer molecule. Next, the polymer is farther
equilibrated with an amine selected from the group consisting of
"Ethomeen C25", triamylamine, triethylamine, and
di-(2-ethylhexyl)amine. The amine reacts with the ureacted carboxyl
groups to impart lipophilic properties to a portion of the polymer
molecule.
Prepared separately is an "oil phase" by dissolving the unsaturated
organic compound in a polar solvent, such as those listed on page
17. To this solution is added a nonionic surfactant that is soluble
in the polar solvent. Thus, the surfactant should have a
hydrophilic-lipophilic balance number of at least 11, and while any
of the nonionic surfactants listed on page 15 can be utilized,
polysorbate 80 is preferred in all cases. The quantity of
surfactant utilized can vary from as little as 1 part by volume of
surfactant to 5 parts by volume of the active compound when the
final product is to be in powder form to 2 parts by volume of
surfactant to 1 part of the compound when a concentrated emulsion
is to be formed. At this point, the "oil phase" prepared as
described above is combined with the aqueous solution of the
polymer to form an aqueous emulsion of the unsaturated organic
compound.
In the event l-naphthyl N-methyl carbamate is the compound being
emulsified, and methyl alcohol is the solvent in which this
compound is dissolved, it has been found desirable, just prior to
combining the "oil phase" with the aqueous solution, to add to the
oil phase the same amine used to partially equilibrate the polymer
in a quantity equal to the quantity used in the polymer
equilibration. Similarly, when l-naphthyl N-methyl carbamate is the
compound being emulsified, and dimethyl sulfoxide is the solvent
used to prepare the "oil phase," it is preferable to add to this
phase, immediately prior to the combining step, triethylamine in a
quantity equal to the quantity of amine used to equilibrate the
polymer.
The emulsion itself may be utilized to apply the unsaturated
organic compound in those cases where a relatively high
concentration of the compound is desired. Concentrations in excess
of 6% by weight of the active ingredient can be prepared in this
manner and it is found that the biologically active compound
exhibits three to four times the stability against light, acid, and
alkali deterioration as an ordinary emulsion of the same
compound.
When it is desired to convert the emulsion to a concentrated paste,
a saline solution is added to the emulsion to precipitate the
polymer complex of the active compound. The supernatant liquid is
decanted and the resulting paste is normally from 30% - 35% by
weight active ingredient. To convert the paste to a powder, the
liquid is removed by evaporation or desiccation. In either paste or
powder form, the final product can be easily reemulsified and is
again three to four times as stable against light, acid, and alkali
deterioration as an ordinary emulsion of the same compound.
The following example is illustrative of the above described
alternative form of the invention.
Example XVII
Carboxypolymethylene (0.26 gm) is dissolved in 80 ml of water and
then equilibrated with approximately 0.3 gm (dry) of NaOH. Next
approximately 0.3 gm of Ethomeen C25 is added to complete
equilibration. This completes the aqueous phase.
The oil phase is prepared by dissolving 10 gm of l-naphthyl
N-methyl carbamate in 50 ml of methyl alcohol and adding 2 ml of
polysorbate 80 surfactant. Before combining the aqueous and oil
phases, 0.3 gm of Ethomeen C25 is added to the oil phase.
At this point, the two phases are combined to form the aqueous
emulsion. Adequate mixing assures a good emulsion although
homogenization equipment can be employed if desired. A 0.1 normal
saline solution is added to the above prepared emulsion to
precipitate out the polymer-complex of the l-naphthyl N-methyl
carbamate. The supernatant liquid is decanted and the resulting
paste is evaporated to a dry powder.
* * * * *